The broad objective of the current proposal was to develop methods for quantifying hepatic glucose production in human subjects without the use of surgical intervention or radioisotopes. In the fourth year of the project, the method for quantifying systematic glucose production rates with glucose-1-C13 tracer was validated in animals, and applied to the measurement of glucose production in adult man and in newborn infants of normal and diabetic women. Maternal hyperglycemia was associated with suppression of systemic glucose production in the newborn infant. In addition, an animal model was developed for examining the effects of maternal diabetes on the capacity for hepatic glucose production in the newborn period. The capacity for glucose production by livers isolated from fasting newborn dogs increased between 0 and 9 hours of age, both in the unstimulated, and in the hormonally stimulated state. Puppies born to a diabetic dog had a diminished capacity for glucose release and for response to hormone. The current proposal will examine the regulatory events which result in diminished glucose production by infants of diabetic mothers, and will initiate the investigation of low-birth-weight infants. BIBLIOGRAPHIC REFERENCES: Kalhan, S.C., Savin, S.M., and Adam, P.A.J. Quantification of glucose turnover with glucose-1-C13 tracer: Attenuated glucose production in newborn infants of diabetic mothers. Abstract: Pediatric Research, 1976 (in press). Kalhan, S.C., Savin, S.M., and Adam, P.A.J. Estimation of glucose turnover with stable tracer glucose-1-C13: Failure of alanine to stimulate glucose production in fasting man. Abstract: Clinical Research, 1976 (in press).